Tacrolimus for the treatment of focal segmental glomerulosclerosis resistant to cyclosporine A

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Sir,We read with great interest the article by Loeffler et al. [1]referring to the efficacy of tacrolimus (TL) in children withrefractory nephrotic syndrome (NS). However, there is littlepublished information on TL treatment of childhood focalsegmental glomerulosclerosis (FSGS) [1, 2]. In this letter,we report on two pediatric patients with cyclosporine A(CsA)-resistant FSGS in whom successful and rapid clinicalremission and reduction in the dose of prednisolone (PSL)were achieved following TL treatment.Case 1 A 9-year-old Japanese boy was referred to ourhospital with a 2-month history of unremitting steroid-resistant proteinuria. A percutaneous renal biopsy revealedlesions characteristic of FSGS. Despite aggressive immu-nosuppressive therapy, such as methylprednisolone pulsetherapy (MPT), and therapy with cyclophosphamide(CPM), mizoribine (MZR) and CsA at the dose of5.0 mg/kg daily [3], the heavy proteinuria persisted forthe next 6 months. The trough blood level of CsA remainedbetween 111 and 316 ng/ml. Intermittent low-densitylipoprotein (LDL) apheresis, followed by oral PSL at thedose of 1.0 mg/kg daily in combination with CsA, provedto be partially effective. However, the patient developedsevere steroid toxicity, including obesity, short stature,cataract, and osteoporosis.Case 2 An 11-year-old Japanese girl was brought to aregional hospital with an 8-day history of generalizededema. Urinalysis revealed a urinary protein excretion levelof 1,153 mg/dl without hematuria. A percutaneous renalbiopsy revealed lesions characteristic of FSGS. AlthoughMPT was administered followed by oral PSL combinedwith CsA at the dose of 3.0 mg/kg daily, heavy proteinuriapersisted for the next 4 months. The trough blood level ofCsA remained between 120 and 257 ng/ml. The patient wasthereafter referred to our hospital for further examinations.A second renal biopsy revealed lesions of mild CsA-relatednephrotoxicity in about 5% of the interstitium. Therefore,CsA was stopped and replaced by high-dose intermittentMZR [4]. LDL-apheresis was also initiated, which provedto be partially effective. However, another relapse of heavyproteinuria occurred 6 months after the admission. Thepatient subsequently developed severe steroid-inducedosteoporosis.TL treatment After obtaining approval from the ethicscommittee at our institution, both patients were treatedwith TL. The initial TL dose was 4 mg daily, administeredin two divided dose (0.1 mg/kg in case 1 and 0.08 mg/kg incase 2). Timing of the commencement of TL from the onsetof NS was 3 years in case 1 and 18 months in case 2. Thetrough blood level of TL remained in the range of between4.6 and 13.3 ng/ml in case 1, while in case 2, the troughblood level of TL remained in the range of between 4.3 and6.5 ng/ml, despite the TL dose was subsequently increasedto 6 mg (0.12 mg/kg).